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Clinical
Pharmacology and Therapeutics, Royal Hallamshire Hospital, Glossop
Road, Sheffield S10 2JF, UK
Correspondence to: Professor Ramsay a.lee{at}sheffield.ac.uk
Accepted 14 September
2000
OBJECTIVE
To determine the
cardiovascular and coronary risk thresholds at which aspirin for
primary prevention of coronary heart disease is safe and worthwhile.
DESIGN
Meta-analysis of four
randomised controlled trials of aspirin for primary prevention. The
benefit and harm from aspirin treatment were examined to determine: (1)
the cardiovascular and coronary risk threshold at which benefit in
prevention of myocardial infarction exceeds harm from significant
bleeding; and (2) the absolute benefit expressed as number needed to
treat (NNT) for aspirin net of cerebral haemorrhage and other bleeding
complications at different levels of coronary risk.
MAIN OUTCOME MEASURES
Benefit from
aspirin, expressed as reduction in cardiovascular events, myocardial
infarctions, strokes, and total mortality; harm caused by aspirin in
relation to significant bleeds and major haemorrhages.
RESULTS
Aspirin for primary
prevention significantly reduced all cardiovascular events by 15%
(95% confidence interval (CI) 6% to 22%) and myocardial infarctions
by 30% (95% CI 21% to 38%), and non-significantly reduced all
deaths by 6% (95% CI
4% to 15%). Aspirin non-significantly
increased strokes by 6% (95% CI
24% to 9%) and significantly
increased bleeding complications by 69% (95% CI 38% to 107%). The
risk of major bleeding balanced the reduction in cardiovascular events
when cardiovascular event risk was 0.22%/year. The upper 95% CI for
this estimate suggests that harm from aspirin is unlikely to outweigh
benefit provided the cardiovascular event risk is 0.8%/year,
equivalent to a coronary risk of 0.6%/year. At coronary event risk
1.5%/year, the five year NNT was 44 to prevent a myocardial
infarction, and 77 to prevent a myocardial infarction net of any
important bleeding complication. At coronary event risk 1%/year the
NNT was 67 to prevent a myocardial infarction, and 182 to prevent a
myocardial infarction net of important bleeding.
CONCLUSIONS
Aspirin treatment for
primary prevention is safe and worthwhile at coronary event risk
1.5%/year; safe but of limited value at coronary risk 1%/year;
and unsafe at coronary event risk 0.5%/year. Advice on aspirin for
primary prevention requires formal accurate estimation of absolute
coronary event risk.
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